Zofenopril Protects Against Myocardial Ischemia-Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability

Autor: Giuseppe Cirino, David J. Polhemus, Erminia Donnarumma, Rajan A.G. Patel, Traci T. Goodchild, Jessica M. Bradley, J. Stephen Jenkins, Stefano Evangelista, Murtuza J Ali, Amy Scarborough, Amanda M. Rushing, David J. Lefer, Kazi N. Islam, Chelsea L. Organ
Přispěvatelé: Donnarumma, E, Ali, Mj, Rushing, Am, Scarborough, Al, Bradley, Jm, Organ, Cl, Islam, Kn, Polhemus, Dj, Evangelista, S, Cirino, G, Jenkins, J, Patel, Ra, Lefer, Dj, Goodchild, Tt.
Rok vydání: 2016
Předmět:
0301 basic medicine
Captopril
Swine
Myocardial Infarction
hydrogen sulfide
030204 cardiovascular system & hematology
Pharmacology
chemistry.chemical_compound
Mice
Random Allocation
0302 clinical medicine
Ramipril
Ischemia
Original Research
Cardioprotection
biology
Reverse Transcriptase Polymerase Chain Reaction
troponin
Cystathionine gamma-lyase
oxidant stre
Nitric Oxide Synthase Type III
Heart
3. Good health
Zofenopril
myocardial ischemia
Anesthesia
Sulfurtransferases
antihypertensive agent
Endothelium/Vascular Type/Nitric Oxide
Swine
Miniature
Cardiology and Cardiovascular Medicine
Blotting
Western
Biological Availability
Cystathionine beta-Synthase
Myocardial Reperfusion Injury
Nitric Oxide
Nitric oxide
ACE/Angiotension Receptors/Renin Angiotensin System
03 medical and health sciences
medicine
Animals
Antihypertensive Agents
Heart Failure
oxidant stress
business.industry
Myocardium
Troponin I
Cystathionine gamma-Lyase
medicine.disease
equipment and supplies
Cystathionine beta synthase
030104 developmental biology
chemistry
Regional Blood Flow
biology.protein
business
Reperfusion injury
Biomarkers
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background Zofenopril, a sulfhydrylated angiotensin‐converting enzyme inhibitor (ACEI), reduces mortality and morbidity in infarcted patients to a greater extent than do other ACEIs. Zofenopril is a unique ACE I that has been shown to increase hydrogen sulfide (H 2 S) bioavailability and nitric oxide ( NO ) levels via bradykinin‐dependent signaling. Both H 2 S and NO exert cytoprotective and antioxidant effects. We examined zofenopril effects on H 2 S and NO bioavailability and cardiac damage in murine and swine models of myocardial ischemia/reperfusion ( I /R) injury. Methods and Results Zofenopril (10 mg/kg PO ) was administered for 1, 8, and 24 hours to establish optimal dosing in mice. Myocardial and plasma H 2 S and NO levels were measured along with the levels of H 2 S and NO enzymes (cystathionine β‐synthase, cystathionine γ‐lyase, 3‐mercaptopyruvate sulfur transferase, and endothelial nitric oxide synthase). Mice received 8 hours of zofenopril or vehicle pretreatment followed by 45 minutes of ischemia and 24 hours of reperfusion. Pigs received placebo or zofenopril (30 mg/daily orally) 7 days before 75 minutes of ischemia and 48 hours of reperfusion. Zofenopril significantly augmented both plasma and myocardial H 2 S and NO levels in mice and plasma H 2 S (sulfane sulfur) in pigs. Cystathionine β‐synthase, cystathionine γ‐lyase, 3‐mercaptopyruvate sulfur transferase, and total endothelial nitric oxide synthase levels were unaltered, while phospho‐endothelial nitric oxide synthase 1177 was significantly increased in mice. Pretreatment with zofenopril significantly reduced myocardial infarct size and cardiac troponin I levels after I /R injury in both mice and swine. Zofenopril also significantly preserved ischemic zone endocardial blood flow at reperfusion in pigs after I/R. Conclusions Zofenopril‐mediated cardioprotection during I /R is associated with an increase in H 2 S and NO signaling.
Databáze: OpenAIRE
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